Coronaviruses

Imke Steffen, Blood Systems Research Institute and University of California San Francisco, San Francisco, California, USA
Graham Simmons, Blood Systems Research Institute and University of California San Francisco, San Francisco, California, USA

Abstract

Coronaviruses are important human and animal pathogens causing respiratory and gastrointestinal infections ranging from mild
to severe. Two highly pathogenic human coronaviruses with high fatality rates, SARS‐CoV and MERS‐CoV, have emerged in different
parts of the world in the recent past causing major public health concerns. Several unique features of coronaviruses make
them likely the candidates for zoonotic transmissions into the human population: (1) their exceptionally large RNA genomes
allow for increased plasticity and diversity, (2) their presence in mammalian (bat) and avian reservoir species with specialised
immune functions and increased mobility facilitates their geographical spread and (3) their sophisticated molecular mechanisms
of viral entry, replication and assembly involving a number of poorly studied viral accessory proteins complicates the development
of suitable therapeutic strategies.

Key Concepts

Coronaviruses contain the largest known viral RNA genomes.

Bats and birds are major reservoirs for coronaviruses.

Two highly pathogenic human coronaviruses, SARS‐CoV and MERS‐CoV, have emerged since the early 2000s.

Coronavirus spike proteins are activated by a variety of proteases, often in a two‐step proteolysis process.

Figure 1. Phylogenetic relationships between selected coronaviruses. Molecular Phylogenetic analysis of full‐length coronavirus RNA‐dependent
RNA polymerase sequences by Maximum Likelihood method. The evolutionary history was inferred by using the Maximum Likelihood
method based on the JTT matrix‐based model. The bootstrap consensus tree inferred from 1000 replicates is taken to represent
the evolutionary history of the taxa analysed. Branches corresponding to partitions reproduced in less than 50% bootstrap
replicates are collapsed. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbour‐Join
and BioNJ algorithms to a matrix of pairwise distances estimated using a JTT model, and then selecting the topology with superior
log‐likelihood value. The analysis involved 29 amino acid sequences. All positions containing gaps and missing data were eliminated.
There were a total of 910 positions in the final dataset. Evolutionary analyses were conducted in MEGA6. For references, see: Jones, D.T., et al., 1992. The rapid generation of mutation data matrices from protein sequences. Computer
Applications in the Biosciences: CABIOS 8, 275–282 and Tamura, K., et al., 2013. MEGA6: Molecular Evolutionary Genetics Analysis,
version 6.0. Molecular Biology and Evolution 30, 2725–2729.

Figure 2. Schematic representation of coronavirus transmission cycles. The coronavirus genera
‐ and β‐coronaviruses originate from bats and infect a number of different mammalian species including humans either directly
or through intermediate hosts. In contrast, the genera γ‐ and
‐coronavirus have evolved separately and are maintained in avian reservoir species and only few mammalian host species have
been identified thus far.

Figure 3. (a) Transmission electron micrograph (TEM) of a number of infectious bronchitis virus (IBV) virions, which are
family members, and members of the genus Coronavirus. The coronavirus derives its name from the fact that under electron
microscopic examination, each virion is surrounded by a ‘corona’ or halo. This is due to the presence of viral spike peplomers
emanating from its proteinaceous capsid. (Content providers: Dr. Fred Murphy and Sylvia Whitfield (CDC). This image is in
the public domain and thus free of any copyright restrictions.) (b) Schematic representation of a murine hepatitis virus particle.
The single‐stranded, positive‐sense RNA genome in complex with the nucleocapsid protein (N) is packaged into the core of the
particle, while the hemagglutinin esterase (HE), spike (S), small envelope (E) and membrane (M) proteins are embedded into
the host cell‐derived membranous envelope.

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